EHD2-mediated restriction of caveolar dynamics regulates cellular fatty acid uptake.
Claudia MatthaeusInes LahmannSéverine KunzWenke JonasArthur Alves MeloMartin LehmannElin LarssonRichard LundmarkMatthias KernMatthias BlüherHannah OlschowskiJulian KompaBritta BrüggerDominik N MüllerVolker HauckeAnnette SchürmannCarmen BirchmeierOliver DaumkePublished in: Proceedings of the National Academy of Sciences of the United States of America (2020)
Eps15-homology domain containing protein 2 (EHD2) is a dynamin-related ATPase located at the neck of caveolae, but its physiological function has remained unclear. Here, we found that global genetic ablation of EHD2 in mice leads to increased lipid droplet size in fat tissue. This organismic phenotype was paralleled at the cellular level by increased fatty acid uptake via a caveolae- and CD36-dependent pathway that also involves dynamin. Concomitantly, elevated numbers of detached caveolae were found in brown and white adipose tissue lacking EHD2, and increased caveolar mobility in mouse embryonic fibroblasts. EHD2 expression itself was down-regulated in the visceral fat of two obese mouse models and obese patients. Our data suggest that EHD2 controls a cell-autonomous, caveolae-dependent fatty acid uptake pathway and imply that low EHD2 expression levels are linked to obesity.
Keyphrases
- fatty acid
- adipose tissue
- obese patients
- insulin resistance
- bariatric surgery
- poor prognosis
- weight loss
- type diabetes
- metabolic syndrome
- high fat diet induced
- high fat diet
- single cell
- mouse model
- gastric bypass
- transcription factor
- machine learning
- stem cells
- weight gain
- skeletal muscle
- electronic health record
- small molecule
- genome wide
- high throughput
- body mass index
- physical activity
- extracellular matrix
- big data
- protein protein